HA4 Ecotoxicogenomics
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() Thyroid hormone receptor expression in blubber biopsies is related to environmental contamination in harbour seals.

Tabuchi, Maki 1, 2, Veldhoen, Nik2, Dangerfield, Neil1, Helbing, Caren2, Ross, Peter1, 1 Institute of Ocean Sciences, Fisheries and Oceans Canada, Sidney, British Columbia, Canada2 Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada

ABSTRACT- Elevated environmental concentrations of persistent organic pollutants (POPs) have been implicated in the disruption of thyroid hormone (TH) physiology in high trophic level wildlife, including marine mammals. We are investigating the relationship between blubber concentrations of POPs and aspects of thyroid hormone physiology in free-ranging harbour seals (Phoca vitulina) sampled at five sites in British Columbia (BC), Canada and Washington State (WA), U.S.A. TH functions mainly by binding to nuclear thyroid hormone receptors (TR alpha and TR beta) in target tissues and by modulating gene expression programs and cell fate. Despite the central role that TH plays in normal development, little is known about the mechanism by which POPs target TH action. In this study, we isolated harbour seal TR alpha and TR beta genes from blubber and designed gene-specific probes for use in a quantitative real-time polymerase chain reaction (QPCR) assay. This represents the first demonstration of TR sequences from a marine mammal. We measured TH levels in serum and TR mRNA expression in blubber and skin biopsies obtained from seal pups. While TR expression varied with blubber depth, the intermediate depth examined was found to be most reliable when evaluated against an internal tissue control (ribosomal protein L8). Both TR alpha and TR beta expression were positively associated with degree of site contamination, with heavily contaminated (PCBs plus total dioxin toxic equivalents) seals in Puget Sound (WA) having the highest TR expression, and the least contaminated seals in the remote Queen Charlotte strait (BC) having the lowest. In contrast, circulating serum TH (thyroxine) levels were lowest in seals from Puget Sound compared to seals from the other locations. TR gene expression measurements in biopsies may therefore represent a useful and minimally-invasive biomarker for assessing TH- associated disruption in marine mammals.

Key words: Thyroid hormone, Thyroid hormone receptor, Marine mammals, Persistent organic pollutants

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